Domoic Acid (DA) is a naturally occuring marine toxin that is responsible for Amnestic Shellfish Poisoning (ASP), or even death in humans who consume tainted shellfish. Within the past decade, rising levels of DA on the US west coast has been responsible for outbreaks of toxicity affecting fish, shellfish, shorebirds and sealions. The highest levels of DA ever recorded in the United States (exceeding established safety levels of 20 ppm by more than 280 ppm) were found in harvesting beaches of several subsistence level Native American Tribes within the past four years. The purpose of this five year longitudinal cohort study of 625 Native Americans is to determine the incidence and prevalence of domoic acid related illness in this at-risk group and to identify both exposure and host factors associated with the occurrence of illness, including the effects of repeated "low" level exposure. Participants will be randomly selected from four US and one Canadian Tribe and will represent five at-risk age groups: infants, young children, older children, adults and geriatric. They will have varying levels of exposure and will be studied annually with standard, age-appropriate neuropsychological measures of memory and cognition. Exposure will be uniformly determined through 1) bi-monthly shellfish sampling and standard detection measures for DA conducted by NOAA from June to October of each year and 2) standardized dietary and shellfish consumption intake measurement. The study design will also enable us to determine the percent of the population with one or more risk factors, examine threshold levels of exposure for five different age groups, re-examine current FDA established safety levels for different age groups, and study the impact of early exposure on child development. Our ultimate goal is to provide a rational basis for shellfish regulation and preventive education to disproportionately exposed and medically underserved Native American communities. [unreadable] [unreadable]